The main purpose of our proposal is to develop a novel sample introduction interface to matrix-assisted laser/desorption (MALDI) mass spectrometry (MS) to achieve not only a radical simplification of the sample handling system but also high throughput analysis. An atmospheric pressure (AP) infrared (IR) MALDI ion source in which ions are produced at normal atmospheric pressure will be used in contrast to conventional MALDI where ions are formed inside a vacuum system. AP-MALDI demonstrated recently using ultraviolet (UV) lasers has shown sensitivity comparable to that of conventional MALDI, a large tolerance to the laser energy, and minimal fragmentation of analyte ions. A drawback of AP-UV-MALDI was the high probability of formation of the analyte-matrix clusters. To overcome this problem we will use a miniature tunable lR laser which has also been shown to produce significantly lesser fragmentation than UV-MALDI. Given the excellent absorption of organic compounds in the lR spectral range the proposal makes possible direct coupling of liquid separation techniques to MALDI mass analyzers, thus, the perspective of having both MALDI and electrospray ion sources for liquid analysis on the same mass analyzer becomes very feasible. PROPOSED COMMERCIAL APPLICATIONS: Atmospheric Pressure IR-MALDI ion source can be the best alternative to the traditional ion sources for interfacing mass spectrometers to liquid separation techniques as well as for off-line analysis. This method has many biological and biomedical applications in research labs, hospitals, industry, and defense where analysis of proteins, peptides, DNA & RNA is utilized. Commercialization of the method by SESI is straightforward.